Building the process-drug–side effect network to discover the relationship between biological Processes and side effects

<p>Abstract</p> <p>Background</p> <p>Side effects are unwanted responses to drug treatment and are important resources for human phenotype information. The recent development of a database on side effects, the side effect resource (SIDER), is a first step in documenting the relationship between drugs and their side effects. It is, however, insufficient to simply find the association of drugs with biological processes; that relationship is crucial because drugs that influence biological processes can have an impact on phenotype. Therefore, knowing which processes respond to drugs that influence the phenotype will enable more effective and systematic study of the effect of drugs on phenotype. To the best of our knowledge, the relationship between biological processes and side effects of drugs has not yet been systematically researched.</p> <p>Methods</p> <p>We propose 3 steps for systematically searching relationships between drugs and biological processes: enrichment scores (ES) calculations, t-score calculation, and threshold-based filtering. Subsequently, the side effect-related biological processes are found by merging the drug-biological process network and the drug-side effect network. Evaluation is conducted in 2 ways: first, by discerning the number of biological processes discovered by our method that co-occur with Gene Ontology (GO) terms in relation to effects extracted from PubMed records using a text-mining technique and second, determining whether there is improvement in performance by limiting response processes by drugs sharing the same side effect to frequent ones alone.</p> <p>Results</p> <p>The multi-level network (the process-drug-side effect network) was built by merging the drug-biological process network and the drug-side effect network. We generated a network of 74 drugs-168 side effects-2209 biological process relation resources. The preliminary results showed that the process-drug-side effect network was able to find meaningful relationships between biological processes and side effects in an efficient manner.</p> <p>Conclusions</p> <p>We propose a novel process-drug-side effect network for discovering the relationship between biological processes and side effects. By exploring the relationship between drugs and phenotypes through a multi-level network, the mechanisms underlying the effect of specific drugs on the human body may be understood.</p

Mortalités et géographie de la santé dans le Nord et le Pas-de-Calais

All causes mortality of the Region Nord -Pas-de-Calais is well higher that the french average but this excess of mortality varies with causes of death. This excess is especially high for mortality due to some cancers (oesophagus and upper aerodigestives tracts), respiratory diseases and alcohol -related diseases in men and alcohol -related diseases in women. At the infraregional scale, the «Bassin minier» can be lesly distinguished by high alcohol related and respiratory mortality in men. This spatial pattern could be due to specific local human and socioeconomic factors.La mortalité régionale du Nord -Pas-de-Calais est nettement supérieure à la moyenne française mais cette surmortalité varie selon les causes de décès. Elle est particulièrement nette pour les cancers de l'œsophage et des voies aérodigestives supérieures, les maladies respiratoires et les maladies attribuées à l'alcool. A l'échelle infrarégionale, le Bassin minier se distingue nettement du reste de la région par une importante mortalité, d'origine respiratoire ou alcoolique. Les spécificités humaines, économiques et sociales locales semblent jouer un rôle non négligeable dans cette focalisation géographique.Lacoste Olivier, Lahoute C., Declercq C. Mortalités et géographie de la santé dans le Nord et le Pas-de-Calais. In: Hommes et Terres du Nord, 1990/2. Géographie de la scolarité et de la santé. pp. 117-126

Striated muscle activator of Rho signalling (STARS) is a PGC-1α/oestrogen-related receptor-α target gene and is upregulated in human skeletal muscle after endurance exercise

Exercise improves the ability of skeletal muscle to metabolise fats and sugars. For these improvements to occur the muscle detects a signal caused by exercise, resulting in changes in genes and proteins that control metabolism. We show that endurance exercise increases the amount of a protein called striated muscle activator of Rho signalling (STARS) as well as several other proteins influenced by STARS.We also show that the amount of STARS can be increased by signals directed from proteins called peroxisome proliferator-activated receptor gamma co-activator 1-&alpha; (PGC-1&alpha;) and oestrogen-related receptor-&alpha; (ERR&alpha;). We also observed that when we reduce the amount of STARS in muscle cells, we block the ability of PGC-1&alpha;/ERR&alpha; to increase a gene called carnitine palmitoyltransferase-1&beta; (CPT-1&beta;), which is important for fat metabolism. Our study has shown that the STARS pathway is regulated by endurance exercise. STARS may also play a role in fat metabolism in muscle.<br /

Rebamipide ameliorates atherosclerosis by controlling lipid metabolism and inflammation

The oral administration of rebamipide decreased plaque formation in atherosclerotic lesions as well as the markers of metabolic disorder in ApoE-deficient mice with atherosclerosis. Pro-inflammatory cytokines were also suppressed by rebamapide. In addition, the population of Th17 was decreased, whereas Treg was increased in the spleen of rebamipide-treated ApoE deficient mice. Rebamipide also ameliorated the severity of obese arthritis and has the capability to reduce the development of atherosclerosis by controlling the balance between Th17 and Treg cells. Thus, rebamipide could be a therapeutic agent to improve the progression of inflammation in metabolic diseases